A thermal cycler for implementing chemical and/or biological reactions comprising a body for accommodating one or more reaction vessels and a cover is disclosed, for example, in EP 1 013 342. Therein, the cover for closing the base body containing the reaction vessels is rigid and is placed on top of said body. In order to seal off the reaction vessels, an electrical positioner is actuated so that a moveable part of the rigid cover is pressed against the caps of the reaction vessels. The use of a rigid cover is suitable for a microtiter plate having identical reaction vessels with compressible caps. However, this rigid set-up is not suited to be adjusted in case reaction vessels (including caps) of different heights are present in the same array, for example due to manufacturing tolerances, since the pressure may not be evenly distributed over all wells or vessels. Also, the set-up as described in EP '342 may lead to uneven evaporation or condensation phenomena at the different reaction sites due to uneven (inhomogeneous) application of pressure, in particular at the fringe areas of the array.
A similar disclosure can be found in U.S. Pat. No. 5,475,610 comprising one embodiment (FIG. 19) according to which a rigid “platen” is displaced and pressed against an array of reaction vessels to keep said reaction vessels in position during thermocycling. The disclosure of U.S. '610 fails to teach how to balance potential differences in height and/or size of the reaction vessels since U.S. Pat. No. 5,475,610 preferably uses a rigid platen and exclusively deals with multiple well plates. The sample arrangement of U.S. '610 also does not take into account problems associated with an uneven pressure distribution caused by the rigid plate leading to uneven evaporation condensation effects at the lid. This holds in particular as the sealing principle of U.S. '610 relies on the presence of resiliently deformable caps. As another example of prior art, U.S. Pat. No. 6,703,236 relates to a device similar to U.S. '610 having similar features and, therefore, similar drawbacks.
WO 2006/002226 relates to a system for thermal cycling samples. The system comprises a thermal cycling device having a plurality of cavities adapted to receive at least a portion of a plurality of sample wells and a heated lid. The system of WO '226 further comprises at least one pneumatic driver connected to the heated lid. The pneumatic driver is configured to position the heated lid in a closed position and an open position, and to move the heated lid between the closed position and the open position. The system also comprises at least one pneumatic actuator connected to the pneumatic driver. The pneumatic actuator is configured to actuate the pneumatic driver to automatically position and move the heated lid between the closed position and the open position. The system also comprises at least one controller coupled to the pneumatic actuator. The controller configured to provide at least one of an electric signal and pneumatic signal to the pneumatic actuator to actuate the pneumatic driver. The teaching of WO '226, however, is restricted to a rigid heated lid and therefore leads to the very same problems in regard to uneven pressure distribution over the sample wells and therefore to (uneven) evaporation and condensation patterns, in particular at the fringes of the well plates.
WO 03/059517 discloses a method of applying a temporary seal to a reaction vessel for use in a water-bath thermocycler. Said temporary seal is achieved by placing a “sealing pad” against an operative surface of the reaction vessels and applying pressure to seal said pad against the operative surface of said vessels. WO '517 relates to a completely different basic design of thermal cyclers as the systems discussed above in that the system of WO '517 does not comprise a heated cover and that the plates are completely immersed in the temperature control medium. WO '517 also fails to address the problem of condensation and/or uneven evaporation and condensation at the fringes of the microtiter plates.
U.S. Pat. No. 6,518,060 relates to a “cover pad” used for covering a plurality of reaction wells open to the other surface and configured in a plate-shaped body provided for implementing chemical and/or microchemical reactions. Said cover pad is made of an elastomer comprising a soft backing which is provided with a rigid backing plate for stiffness. Due to the use of a rigid plate, the same problems arise in regard to condensation and evaporation in the lid area as discussed above.
In view of the prior art in the field, it is an object of the present invention to provide a device and a method according to which at least one sample, preferably contained in a vessel, is covered by means for covering in a manner so that potential evaporation of the sample or components of the sample is avoided or minimized and/or that condensation of vaporizable fluids of said sample on said means for covering and/or on the caps/lids of reaction vessels (if reaction vessels are used) and/or on the top part of sample wells (if multi-well plates or blocks are used) is minimized or avoided. In particular, inhomogenities in respect to evaporation and/or of condensation between different vessels/wells in an array of vessels or wells should be avoided/minimized. The latter applies in particular if a plurality of samples and/or vessels/wells is covered.
Furthermore, it is a preferred object according to the present invention to provide a device and a method that minimize or avoid to the damaging and/or deformation of reaction vessels and/or sample plates/blocks with wells during the process of covering the same. Preferably, such damage or deformation should be avoided/minimized if the reaction vessels and/or their caps and/or wells do not have the same height (tolerance).